The Porcine Reproductive and Respiratory Syndrome virus (vPRRS) is an enveloped virus belonging to the RNA group, Arteriviridae family, Arterivirus genus. Its size ranges around 460 nm and its viral genome is comprised by a RNA strand in the positive sense, which results in 7 open reading frames (ORF), ORF1a, ORF1b, ORF2-ORF7, which in turn results in the assembling of 7 structural proteins (gp 2a, 2b-5, M and N) and at least 13 non-structural proteins (nsp 1a, nsp 1b-nsp 12), each one with specific functions forming the vPRRS. This virus shows an immunomodulatory behavior when selectively infects the monocyte/macrophage cell line in charge of starting the immune response and of participating in the direction of the immune response, inter alia. The virus has proven ability to alter the immune response by decreasing the gamma interferon (IFNγ) production, and the late production of neutralizing antibodies, and the production of immunological decoys (Yoo et al., 2009; Sang et al., 2009; Patel et al., 2009; Chen et al., 2009; Lalit, 2009). Since vPRRS has a high antigenic variability, it has been difficult to use the traditional method based on various vaccination strategies to combat it. Because of this, worldwide efforts are being made to develop a biological able to combat the diffusion of the infection and the effects thereof, being the genetic manipulation products of the virus the best options to achieve this (Lara, 2010). In this sense, the viral subunits which could give any kind of protection are being also studied, the use of ORF 5 and ORF 6 has shown good expectations because they are responsible, at least in part, for the virus virulence (Kim et al., 2009; Zuckerman et al., 2007), proving that immunity is achieved with live (replicating) products as these are the only ones giving protection in a challenge, this protection being measured by the decrease in post-challenge viraemia. In 2005, ORF 5 mutants were developed by modifying their glycosilation and they were tested as immunogens, finding that the GP5 hypo-glycosilation increases the ability of the vPRRS to induce in vivo neutralizing antibodies (Ansari et al., 2005).
In the specific case of ORF 5, the region between the amino acid residues 1-25 has a high variability among American and European isolates, while the hypervariable region of the strain regions in each continent is grouped between amino acids 26 and 39, near the amino acid terminal sequence.
The change in the ORF 5 sequence may result in atypical outbreaks of the disease as the swine abortion and mortality syndrome (SAMS), or the “high fever” syndrome seen in China (Ferrari et al, 2003; Martelli, 2003).
The vaccine against PRRS currently commercialized contains an attenuated virus, however, it has the disadvantage of having the possibility of infecting the pigs, resulting in disease development and immunological damage, mainly in naive animals (highly susceptible without previous exposition); additionally, it has been shown that this vaccine virus mutates and can recombine itself with the circulating field viruses, thus creating new genetic variants of the virus. Likewise, studies have been made showing that the live attenuated vaccine is not completely efficient to prevent the disease, also, previously it has been shown that the anti-vPRRS antibodies are involved in the amplification mechanism of the antibodies dependent enhancement (ADE) and/or in immunopathology caused by vPRRS (Thanawongnuwech and Suradhat, 2010), which could cause that, contrary to the expectation, the vaccinated animals become more susceptible to the effects of the PRRS disease.
Due to the above, there are several patents related to recombinant vaccines against this disease.
U.S. Pat. No. 7,722,878 discloses recombinant vaccines against PRRS, consisting of a vector comprising an ORF 1 portion of the vPRRS, alone or combined with another ORF. These vaccines are useful to induce an immune response in animals, and to prevent and decrease the condition severity and symptoms caused by a vPRRS infection. In order to determine the efficiency of these vaccines, the number of lung lesions, characteristic of vPRRS, was measured, achieving a decrease in said lung lesions up to 47%.
In U.S. Pat. No. 5,888,513, recombinant proteins corresponding to ORF2-ORF7 of a vPRRS isolated in Spain are disclosed, which are produced in a baculovirus expression system, and which can be used in vaccines formulation.
Chinese Patent Applications Nos. CN1554766A and CN1800375A describe recombinant vaccines against PRRS, which use an adenovirus as a vector. Likewise, Chinese Patent Application No. CN1778926A disclose an ORF 5 modified gene of the vPRRS, which can be used in the preparation of a vaccine against this disease.
In U.S. Pat. No. 7,041,443, virus, polynucleotides and polypeptides of the European type PRRS are described, which may be used in the preparation of immunogenic compositions, which consist in an attenuated or inactivated vPRRS including a polynucleotide selected from several sequences.
On the other hand, U.S. Pat. No. 6,207,165 discloses a multivalent vaccine formula for pig vaccination against pathogen agents involved in reproductive and/or respiratory pathologies, one of them being PRRS. The vaccine includes at least three types of vaccines, each one comprising a plasmid and a gene with a porcine pathogen valence, which in case of PRRS can be the E, ORF 3 or M genes.
Finally, U.S. Pat. No. 5,998,601 discloses VR-2332 strain nucleotide sequences of vPRRS, which can code for ORFs or fragments thereof, as well as vaccines derived thereof.
In spite of the above, although the vaccines described in the state of the art have served to attenuate the effects of the disease, up to date a level of protection against vPRRS that is sufficient for an effective disease control has not been achieved.